UMOD
Uromodulin
Also known as: UROM_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P07911
- Gene
- UMOD
- Ensembl
- ENSG00000169344
- Chromosome
- 16
- Canonical length
- 640 aa
- Protein class
- Disease related genes, Human disease related genes, Plasma proteins, Predicted membrane proteins, Predicted secreted proteins
- Secretome location
- Secreted in other tissues
- Quaternary structure
- Homodimer
OverviewNCBI Gene
The protein encoded by this gene is the most abundant protein in mammalian urine under physiological conditions. Its excretion in urine follows proteolytic cleavage of the ectodomain of its glycosyl phosphatidylinosital-anchored counterpart that is situated on the luminal cell surface of the loop of Henle. This protein may act as a constitutive inhibitor of calcium crystallization in renal fluids. Excretion of this protein in urine may provide defense against urinary tract infections caused by uropathogenic bacteria. Defects in this gene are associated with the renal disorders medullary cystic kidney disease-2 (MCKD2), glomerulocystic kidney disease with hyperuricemia and isosthenuria (GCKDHI), and familial juvenile hyperuricemic nephropathy (FJHN). Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2013]
Canonical amino-acid sequenceUniProt
640 residues, UniProt reviewed canonical sequence.
>P07911|UMOD
1 MGQPSLTWML MVVVASWFIT TAATDTSEAR WCSECHSNAT CTEDEAVTTC TCQEGFTGDG
61 LTCVDLDECA IPGAHNCSAN SSCVNTPGSF SCVCPEGFRL SPGLGCTDVD ECAEPGLSHC
121 HALATCVNVV GSYLCVCPAG YRGDGWHCEC SPGSCGPGLD CVPEGDALVC ADPCQAHRTL
181 DEYWRSTEYG EGYACDTDLR GWYRFVGQGG ARMAETCVPV LRCNTAAPMW LNGTHPSSDE
241 GIVSRKACAH WSGHCCLWDA SVQVKACAGG YYVYNLTAPP ECHLAYCTDP SSVEGTCEEC
301 SIDEDCKSNN GRWHCQCKQD FNITDISLLE HRLECGANDM KVSLGKCQLK SLGFDKVFMY
361 LSDSRCSGFN DRDNRDWVSV VTPARDGPCG TVLTRNETHA TYSNTLYLAD EIIIRDLNIK
421 INFACSYPLD MKVSLKTALQ PMVSALNIRV GGTGMFTVRM ALFQTPSYTQ PYQGSSVTLS
481 TEAFLYVGTM LDGGDLSRFA LLMTNCYATP SSNATDPLKY FIIQDRCPHT RDSTIQVVEN
541 GESSQGRFSV QMFRFAGNYD LVYLHCEVYL CDTMNEKCKP TCSGTRFRSG SVIDQSRVLN
601 LGPITRKGVQ ATVSRAFSSL GLLKVWLPLL LSATLTLTFQLocalizationUniProt · AlphaFold · HPA
Whether an antibody against UMOD can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.34
- Highest tissue expression
- 2,127 nTPM
Expression across tissuesHPA
Tissue
- kidney: 2,127 nTPM
- pancreas: 4.1 nTPM
- cerebral cortex: 2 nTPM
- stomach: 2 nTPM
- colon: 1.4 nTPM
- prostate: 0.8 nTPM
Single-cell type
- loop of henle epithelial cells: 1,188 nCPM
- podocytes: 96 nCPM
- proximal tubule cells: 92 nCPM
- renal collecting duct intercalated cells: 89 nCPM
- distal convoluted tubule cells: 77 nCPM
- renal connecting tubule cells: 61 nCPM
Immune cell
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
- MAIT T-cell: 0 nTPM
Brain region
- hypothalamus: 0.1 nTPM
- amygdala: 0 nTPM
- basal ganglia: 0 nTPM
- cerebellum: 0 nTPM
- cerebral cortex: 0 nTPM
- choroid plexus: 0 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about UMOD.
Disease | AllUniProt
Conditions UMOD is implicated in, by any mechanism.
- Tubulointerstitial kidney disease, autosomal dominant 1 (ADTKD1) MIM:162000
Disease | GeneticClinVar
106 pathogenic / likely-pathogenic of 624 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Familial juvenile hyperuricemic nephropathy type 1
- UMOD-related disorder
- Autosomal dominant medullary cystic kidney disease with or without hyperuricemia
- Inborn genetic diseases
- Renal cyst
ReferencesPubMed · IEDB
Publications for UMOD from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
2 publications
- A Uromodulin Mutation Drives Autoimmunity and Kidney Mononuclear Phagocyte Endoplasmic Reticulum Stress.
2020 · Am J Pathol · RCR 0.4 · 7 citations - Antibodies to Tamm-Horsfall urinary glycoprotein in patients with urinary tract infection, reflux nephropathy, urinary obstruction and paraplegia.
1984 · Contrib Nephrol · RCR 0.3 · 9 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.25
- gnomAD pLI
- 0
- gnomAD missense Z
- 1
- DepMap mean gene effect
- -0.04
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- antibacterial innate immune response
- apoptotic signaling pathway
- autophagy
- cellular defense response
- cellular response to unfolded protein
- collecting duct development
- connective tissue replacement
- defense response to Gram-negative bacterium
- endoplasmic reticulum organization
- ERAD pathway
- gene expression
- glomerular filtration
- heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
- inflammatory response
- intracellular calcium ion homeostasis
- intracellular chloride ion homeostasis
- intracellular phosphate ion homeostasis
- intracellular sodium ion homeostasis
- juxtaglomerular apparatus development
- leukocyte cell-cell adhesion
- lipid metabolic process
- metanephric ascending thin limb development
- metanephric distal convoluted tubule development
- metanephric thick ascending limb development
- micturition
- multicellular organismal response to stress
- negative regulation of cell population proliferation
- neutrophil migration
- organ or tissue specific immune response
- potassium ion homeostasis
- protein folding
- protein localization to extracellular region
- protein localization to vacuole
- protein transport into plasma membrane raft
- regulation of blood pressure
- regulation of protein transport
- regulation of urine volume
- renal sodium ion absorption
- renal urate salt excretion
- renal water homeostasis
- response to lipopolysaccharide
- response to water deprivation
- response to xenobiotic stimulus
- RNA splicing
- tumor necrosis factor-mediated signaling pathway
- urate transport
- urea transmembrane transport
- citric acid secretion
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
- EGF-type aspartate/asparagine hydroxylation site
- EGF-like domain
- Zona pellucida domain
- EGF-like calcium-binding domain
- Growth factor receptor cysteine-rich domain superfamily
- Zona pellucida domain, conserved site
- EGF-like calcium-binding, conserved site
- NELL2-like, EGF domain
- Zona pellucida, ZP-C domain
- Zona pellucida domain, chordate-type
- NOTCH1, EGF-like calcium-binding domain
- ZP-C domain
- ZP-N domain
- UMOD/GP2/OIT3-like, D8C domain
- ZP-C domain
- Calcium-binding EGF domain
- EGF domain
- Uromodulin-like, D8C domain
- ZP-N domain
KeywordsUniProt
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads UMOD as an antibody target. Whether an autoantibody or antibody against UMOD could matter depends on whether native UMOD is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
UMOD is annotated at the cell surface, where native UMOD is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label UMOD as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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